薬理と治療
Volume 41, Issue 4, 2013
Volumes & issues:
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扉・目次
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BOOK PREVIEW
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【臨床研究を正しく評価するにはDr. ファーバーグが教える26 のポイント】 <第2 回>ランダム化比較試験の短所は何か?
41巻4号(2013);View Description Hide Description
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SERIES プラセボについて考える
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BRIEF COMMUNICATION
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カキエキスのアルコール代謝促進作用
41巻4号(2013);View Description Hide DescriptionOral administration of the water extract of Crassostera gigas(1 g/kg body weight, 30 min before)significantly suppressed the elevation of blood ethanol and acetaldehyde levels after the administration of ethanol(4 g/kg)in male Wistar rats(6 weeks of age), indicating that the Crassostera gigas extract should contain some active constituents that accelerate alcohol metabolism in the rats.
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ORIGINAL ARTICLES
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フェキソフェナジン塩酸塩の肥満細胞活性化抑制作用
41巻4号(2013);View Description Hide DescriptionObjectives Fexofenadine hydrochloride(FEX)is well known to be a non-sedative histamine H1 receptor antagonist and used for the treatment of the allergic diseases, such as pllinosis and atopic dermatitis with remarkable success. However, the influence of FEX on mast cell activation, especially cytokine production is not fully understood. The present study, therefore, was undertaken to examine the influence of FEX on cytokine production from mast cells by using a cell culture technique in vitro. Methods Spleen cells obtained from BALB/c mice were cultured in the presence of various concentrations of FEX. The number of mast cells were counted with alcian blue staining on days 7, 12, 16, 21. Peritoneal exudate mast cells obtained from BALB/c mice were sensitized with mouse IgE specific for ovalbumin(OVA). The sensitized mast cells were stimulated with 10 ng/mL OVA in the presence of various concentrations of FEX for 24 hours. The levels of angiogenic factors, keratinocyte derived chemokine(KC), vascular endothelial growth factor(VEGF)and tumor necrosis factor-α(TNF-α), in culture supernatants were examined by ELISA. Results FEX did not inhibit mast cell growth from mouse spleen cells, even when 500 ng/mL of the agent was added to the cell cultures. On the other hand, FEX significantly suppressed the ability of mast cells to produce KC, VEGF and TNF-α in response to antigenic stimulation. The minimum concentration of the agent that caused significant suppression was 200 to 250 ng/mL, which is similar to therapeutic blood levels. Conclusion These results strongly suggest that the suppressive activity of FEX on angiogenic factor production consists, in part, of a therapeutic mode of action of the agent on allergic diseases such as pollinosis and atopic allergy. -
アジュバント関節炎ラットにおける新規抗リウマチ薬イグラチモドとメトトレキサートの併用効果
41巻4号(2013);View Description Hide DescriptionObjectives Iguratimod(IGU), a novel disease-modifying antirheumatic drug, was approved for the treatments of rheumatoid arthritis(RA)in 2012. A clinical study has shown important therapeutic evidence that IGU in combination with methotrexate(MTX)was efficacious and had a manageable safety profile. Therefore, using adjuvant-induced arthritis(AIA)model, we examined the combined effects of IGU with MTX focusing on anti-arthritic effects and anemia as a side effect. Methods AIA was induced by injection with M. tuberculosis to the hind paw in rats and evaluated by measurement of paw volume. The bone destruction was assessed with the Xray photographs. Peripheral erythrocytes and reticulocytes were counted to evaluate the anemia. Results In prophylactic dose regimen on AIA, MTX at 0.3 mg/kg inhibited the arthritis of both hind paws but induced the anemia, and at 0.1 mg/kg also decreased reticulocytes. Inhibitory effect of MTX on the arthritis apparently weakened at 0.1 mg/kg or less. When combined with IGU at 3 mg/kg, MTX at 0.1 mg/kg or 0.07 mg/kg was able to suppress the arthritis on both hind paws, without coursing anemia. When IGU was combined with a low dose of MTX from day 18, more marked inhibitions of swelling were observed compared with MTX alone on day 25. When MTX was exchanged to IGU on day 18, the swelling was significantly improved. Conclusion Our results indicate that the combination of IGU with a low dose of MTX brings in beneficial effects in AIA, suggesting that similar efficacy would be expected in RA patients. -
高齢者におけるシロスタゾール投与時の心拍数に与える併用薬の影響に関する研究
41巻4号(2013);View Description Hide DescriptionCilostazol is used widely as antiplatelet agents. However, the tolerability is decreased for typical side effects caused by its action mechanism. In our hospital, Mie Heart Center, the discontinuation rate of cilostazol treatment due to palpitation or tachycardia was higher in the geriatric patient group than it in the non-geriatric patient group. In the combined treatment with diltiazem hydrochloride which has effect of lowering the heart rate, a trend to decrease in heart rate was shown in the geriatric patient group from a month later. But there was no significant difference. In the combined treatment with beta-blockers, no significant changes in heart rate was shown at early term in both groups, and significant elevated heart rate(P<0.05)was shown only in the geriatric patient group after 1 month to 12 months in comparison with early term. We concluded that it is important to check the heart rate for particularly geriatric patients in case of cilostazol treatment. -
前向きコホート研究データに基づく関節リウマチ治療における生物学的製剤の薬剤経済分析
41巻4号(2013);View Description Hide DescriptionBackground Rheumatoid arthritis (RA) is accompanied by a large societal economic burden. The cost-effectiveness of treatment with specific sequences of biologic agents(biologics)based on trials has been investigated; however, such studies have not adequately considered biologics utilization under real-life conditions, in which treatment conditions were not highly controlled and various sequences of biologics were used. Therefore, the cost-effectiveness of selecting any biologics was investigated using the RA cohort database of the Institute of Rheumatology, Rheumatoid Arthritis(IORRA). Methods A state-transition model-based probabilistic simulation from a societal perspective was conducted. Model parameters were determined using clinical data from 421 patients from the IORRA who had failed at least one disease-modifying anti-rheumatic drug (DMARD)and started either one of four biologics(adalimumab, etanercept, infliximab, and tocilizumab)or methotrexate between April 2008 and April 2011. Patients had no history of biologics use and were matched using the propensity score. A hypothetical population of 10000 patients treated with sequences of three biologics following methotrexate and then best supportive care(BSC), were compared to those starting methotrexate following BSC. Because tocilizumab differs from other biologics in mechanism and showed large decrease of drug price in 2012 in Japan, sequences of three of four biologics(adalimumab, etanercept, infliximab, and tocilizumab)and three of them except for tocilizumab were also considered. Results Clinical data from the IORRA showed no significant differences in disease duration, J-HAQ, EQ-5D, or other patient backgrounds between the matched patients. The incremental cost-effectiveness ratio of treatment sequences with biologics was ¥3817971 or ¥4885450 including tocilizumab or not, respectively, and with more than 80% probability of falling below assumed thresholds of ¥5400000 according to probabilistic sensitivity analysis. Interpretation Biologics are cost-effective for RA patients who failed at least one DMARD based on data from an observational cohort representing daily clinical practice in Japan. -
トウガラシ,ショウガ,シトラスアランティウムを配合した「養生」食品リポレスのヒトエネルギー代謝およびラット脂質代謝に及ぼす影響
41巻4号(2013);View Description Hide DescriptionObjectives Effects of Lipoless, functional food, on energy expenditure in humans and lipid metabolism in rats after exercise were investigated. Methods 1)We conducted a crossover study in 11 healthy volunteers with a 7-days washout period. The participants were administered Lipoless after a meal, twice in the evening and morning, and loaded with an exercise of a bicycle ergometer. The change of sympathetic nerve activity was evaluated by detecting of heart rate variability. Energy expenditure was assessed by indirect calorimetry for 24 h. 2)Male rats were divided into the following 4 groups:Sedentary Control group, Exercise Control group, Sedentary Lipoless group, and Exercise Lipoless group. Lipoless were administered with 2% Lipoless containing diets, and a running exercise was loaded by a treadmill five times a week for 6 weeks of the experimental period. Results 1)Sympathetic nerve activity was enhanced after each meal, and energy expenditure after eating breakfast was significantly higher in Lipoless supplemented group than control group. Exercise had little effect on these changes. 2)Compared with the Sedentary Control group, in all other groups the visceral fat was decreased. A tendency of increase in muscular citrate synthase(CS)activity in the Sedentary Lipoless group, significant increase of CS and 3-hydroxyacyl-CoA dehydrogenase(3-HAD)activities in the Exercise Control group, and CS, 3-HAD, isocitrate dehydrogenase activities in the Exercise Lipoless group were observed compared with the Sedentary Control group. Futhermore, in the Exercise Lipoless group, the body weight gain was less than in the Sedentary Control group. Conclusion These results indicate that Lipoless might be useful food in the prevention of obesity on energy expenditure in short-term intake and on lipid metabolism for long-term.
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CASE REPORT
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爪甲剥離および脱落が遷延した手足口病の成人例
41巻4号(2013);View Description Hide DescriptionThe patient was a 47-year-old man. The major complaints included fever, headache, rashes, and weakness in both legs. Past medical history included atopic dermatitis and bronchial asthma. In mid-July 2011, the patient’s eldest daughter(1 year 4 months old)also developed hand-foot-mouth disease, presenting with fever, followed by palmar and plantar rashes with pain. In late July, the patient developed a fever of 40℃ or higher, headache, and rose-pink rashes with pain that resembles his daughter’s rashes. The rashes occurred not only in the palms and soles but also in the face, neck, and abdomen. The patient also had weakness in both legs. Blood examination revealed an increased inflammatory response. There was a modest increase in serum antibody titer to Coxsackie A16 virus. The fever, headache, rashes, and weakness in both legs subsided rapidly. In early August, however, the patient began to have onycholysis in both fingers and toes. In late November, the nail plate of the right thumb detached from the nail bed. The patient took a long time to recover, and the nail lesions did not resolve until March 2012;until then, the patient experienced difficulties in skilled finger movements and walking. We believe that clinicians should be aware that the symptoms of onycholysis and onychomadesis can last for long periods of time in adult patients with handfoot-mouth disease.
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